Objectives: The Nigerian hypertension guideline (2005) was based on 1999 ISH/WHO and the 2003 Sub-Saharan Africa hypertension guidelines. The changes in the prescribing pattern of physicians before and following the introduction of these guidelines as well as physicians' awareness of the guidelines in Southern Nigeria are unknown. Subjects and Methods: A retrospective study of antihypertensive prescriptions and a cross-sectional descriptive study of the physicians' awareness of the guidelines. The study was carried out at a tertiary health facility in Southern Nigeria and reviewed the case records (1999–2008) of 3379 hypertensive patients who had attended the medical outpatient clinic; it also assessed the awareness of 48 postregistration doctors working in the same hospital using a self-administered questionnaire. Results: Calcium channel blockers were the most prescribed class over the entire period (44.7%–69.2%) while angiotensin-converting enzyme inhibitors prescriptions increased by 325% (11.8%–51.5%). Annual prescriptions of diuretics increased steadily from 38% in 1999 to a peak of 58% in 2005. A total of 37/48 doctors responded, and a high proportion (32/37; 86.5%) were aware of the national guidelines, but only 13/37 (35.1%) were satisfied with the recommendations. Diuretics were stated as the most preferred class of antihypertensive medicines by 26/37 (70.3%) of respondents. Conclusions: The findings suggest disconnect in the prescribers' knowledge of recommendations in the guidelines, their stated preferences for medicines, and the observed findings in the case records. This may be due in part to the observed dissatisfaction of doctors with the guidelines.